Thyroid hormones stimulate growth of normal and malignant cells, and influence metabolism and development. They are, therefore, excellent signals to study as a model for understanding general features of regulation of these processes in mammalian systems. In the proposed studies, we plan to investigate the molecular mechanism of thyroid hormone action. To do so we hope to purify chromatin "receptor" proteins which appear to be mediators of the thyroid hormone response. We plan to study the properties of these receptors in terms of potential biological function and determine the way in which they interact with chromatin and DNA. We also plan to investigate using thyroid hormone-responsive cultured cells whether there are direct hormonal influences on RNA synthesis. We hope to establish cell-free conditions to investigate actions of thyroid hormone and of purified receptors bound by the hormone on RNA synthesis by chromatin. We hope to determine the interrelation of different thyroid-induced responses and gain information as to whether diverse responses such as those on RNA synthesis and transport all occur through nuclear events. We plan to determine the extent to which thyroid hormones stimulate growth or normal and malignant cells and to study the mechanisms of this regulation. Finally, we plan to select cells which vary in their responsiveness to thyroid hormone and to use these to facilitate understanding of thyroid hormone action and genetic regulation.